Di Matteo V, Di Giovanni G, Di Mascio M, Esposito E
Laboratorio di Neurofisiologia, Dipartimento di Farmacologia e Patologia Molecolare, Istituto di Ricerche Farmacologiche 'Mario Negri', Consorzio 'Mario Negri' Sud, 66030 Santa Maria Imbaro, Chieti, Italy.
Brain Res. 2000 May 19;865(1):85-90. doi: 10.1016/s0006-8993(00)02246-0.
In vivo microdialysis and electrophysiological techniques were used to elucidate the role of the 5-HT(2) receptor family on the control of mesolimbic dopaminergic system exerted by serotonin (5-HT). Administration of RO 60-0175 (1 mg/kg, i.p.), a selective 5-HT(2C) receptor agonist, significantly decreased dopamine (DA) release by 26+/-4% (below baseline) 60 min after injection. Moreover, RO 60-0175 (80-320 microg/kg, i.v.) dose-dependently decreased the basal firing rate of DA neurons in the ventral tegmental area (VTA), reaching its maximal inhibitory effect (53.9+/-15%, below baseline) after the dose of 320 microg/kg. The selective 5-HT(2C) receptor antagonist SB 242084 completely blocked the inhibitory action of RO 60-0175 on accumbal DA release and on the firing rate of VTA DA cells. On the contrary, both (+/-)-DOI, a mixed 5-HT(2A/2C) receptor agonist, and the selective 5-HT(2B) agonist BW 723C86, did not affect either DA release in the nucleus accumbens or the firing rate of VTA DA cells. Taken together, these data confirm that central 5-HT system exerts an inhibitory control on the mesolimbic DA system and that 5-HT(2C) receptors are involved in this effect.
采用体内微透析和电生理技术来阐明5-羟色胺（5-HT）对中脑边缘多巴胺能系统的控制中5-HT（2）受体家族的作用。注射选择性5-HT（2C）受体激动剂RO 60-0175（1毫克/千克，腹腔注射）后60分钟，多巴胺（DA）释放量显著降低26±4%（低于基线）。此外，RO 60-0175（80 - 320微克/千克，静脉注射）剂量依赖性地降低腹侧被盖区（VTA）中DA神经元的基础放电率，在320微克/千克剂量后达到最大抑制作用（53.9±15%，低于基线）。选择性5-HT（2C）受体拮抗剂SB 242084完全阻断了RO 60-0175对伏隔核DA释放和VTA DA细胞放电率的抑制作用。相反，5-HT（2A/2C）混合受体激动剂（±）-DOI和选择性5-HT（2B）激动剂BW 723C86对伏隔核中的DA释放或VTA DA细胞的放电率均无影响。综上所述，这些数据证实中枢5-HT系统对中脑边缘DA系统发挥抑制性控制作用，且5-HT（2C）受体参与了这一效应。
